may 2017 page 1 too hs may 2017d.pdf · may 2017 page 1 dr. mclaughlin and col-leagues developed...

Updated Guideline on Brachytherapy

in Prostate Cancer

The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario have issued a joint clinical practice guideline up-date on the use of brachytherapy (BT) for prostate cancer pa-tients. The new guideline was published online in the Journal of Clinical Oncology on March 27th.

BT involves the implantation of radioactive seeds into the pros-tate gland. It is “now the nonsurgical standard of care for the majority of patients with prostate cancer – either by itself or as part of a combination approach,” said Andrew Loblaw, MD, FRCPC, co-chair of the expert panel that developed the guide-line update, who was representing ASCO.

“BT is also more convenient than external-beam radiation [EBRT] and has a much higher chance of curing the disease,” said Dr. Loblaw in a statement. “However, not every patient should have BT, and not all treatment centers are experienced in delivering high-quality BT.”

“For the urologist, who is most often the gatekeeper in terms of first contact with men with prostate cancer, this guideline up-date provides new information they can incorporate into pa-tient counseling and treatment decision making,” said Joseph Chin, MD, FRCSC, co-chair of the expert panel that developed the guideline update and represented Cancer Care Ontario.

“By optimizing treatment selection, which may or may not be BT for a particular patient, outcomes should ultimately be im-proved,” said Dr. Chin in a statement.

(Continued on page 4)

In a phase II study published online in European Urology on February 21st, vessel-sparing radiotherapy (RT) preserved erectile function (EF) in most men with local-ized prostate cancer.

“We would hope that physi-cians understand there is a new standard of successful treatment for prostate can-cer – cure with quality of life,” stated Dr. Patrick W. McLaughlin from University of Michigan in Ann Arbor. “In the past, men seeking cure would potentially have to lose function to accomplish cure, but this study suggests that with close attention to mapping of critical adjacent structures, both cure and quality of life can be accom-plished in the majority of men diagnosed with prostate cancer.”

INSIDE

USPSTF Backs Individualized Prostate Cancer PSA Screening

1

Updated Guideline on Brachytherapy in Prostate Cancer

1

Vessel-Sparing RT Preserves Erec-tile Function in Prostate Cancer

1

Post-RP BCR-Free Survival After Grade Reclassification on AS

2

Urologists vs. Radiation Oncologists on High-Risk Prostate Cancer

2

Men Uncertain About Benefits & Risks of Active Surveillance

2

Doc Moyad’s No Bogus Science: “Vitamin D & VITAL Results”

3

Intermediate-Term Outcomes from AS According to Recurrence Risk

3

Prognostics Significance of a Negative Prostate Biopsy

5

Magnetic Resonance Imaging in Diagnosis of Prostate Cancer in Patients with PSA Level 2-10 ng/mL

5

Doctor Chodak’s Bottom Line 7

MAY 2017 PAGE 1

Dr. McLaughlin and col-leagues developed vessel-sparing RT with the intention of delivering the prescribed RT dose to the prostate with maximal sparing of the bilat-eral corpus cavernosum and internal pudendal artery. They reported five-year pa-tient-reported EF preserva-tion rates and long-term tu-mor control outcomes in 144 men treated with vessel-sparing RT from 2001-2009.

Sixty-one percent received a combination of intensity-modulated RT (IMRT) with brachytherapy (BT), and 33% also received androgen dep-rivation therapy (ADT).

At five years, 35% of men could be sexually active with-out the use of aids, and 53% reported that they were sexually active but required


USPSTF Backs Individualized Prostate Cancer PSA Screening

PROSTATE CANCER HELPLINE: 1-800-808-7866 WWW.USTOO.ORG

Medical opinion about pros-tate cancer (PCa) screening inched closer to harmony with an updated draft recom-mendation from the U.S. Pre-ventive Services Task Force (USPSTF) supporting discus-sion-backed decisions for men, ages 55 to 69. In 2012, the USPSTF recommended against (grade D) routine PSA screening for men of any age.

The position put the USPSTF at odds with the American Urological Association (AUA) and, to a lesser extent, the American Cancer Society

(ACS), both of which sup-ported decision making based on clinician-patient discussion.

The 2017 update more closely aligns their approach with clinician-patient discus-sions about the potential harms and benefits of screening (grade C recom-mendation). The USPSTF sub-mitted the recommendation for public comment that ends May 8th. “New data has come to light, shifting the consensus pendulum in favor of a discussion-based ap-proach, albeit slightly,” said

USPSTF member Alex H. Krist, MD.

“In 2012 and now, there is a close balance of benefits and harms,” stated Krist, of Vir-ginia Commonwealth Univer-sity in Richmond. “Since 2012, there have been a cou-ple of things that emerged that we didn’t know then. With longer follow-up of U.S. and European [screening] trials, we’ve seen that slightly fewer men will die of PCa if they’re screened. That’s a very slight increase.”


Vessel-Sparing Radiotherapy Preserves Erectile

Function in Prostate Cancer

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US TOO INTERNATIONAL PROSTATE CANCER EDUCATION & SUPPORT Hot SHEET – MAY 2017

fined as RT delivered at PSA <0.2 ng/mL), whereas urolo-gists were more likely to pre-fer early or delayed SRT (P <0.0001). ROs were more likely to prefer lower PSA thresholds for initiating SRT (P <0.0001), and more likely to recommend ART in the setting of adverse pathologic features or node-positive disease (P <0.0001). Signifi-cantly more ROs would rec-ommend concurrent andro-gen deprivation therapy (ADT) or pelvic nodal RT in the setting of node-positive or Gleason score 8 to 10 dis-ease (P <0.0001).

Specialty-specific differences were readily elucidated with respect to timing and indica-tions for ART and SRT, as well as for indications for ADT and


To query specialty-specific differences regarding post-operative radiotherapy (RT) for high-risk prostate cancer, an electronic mail survey of radiation oncologists (ROs) and urologists was sent. We sought to maximize the abso-lute response number to capture contemporary prac-tice ethos. The outcome of interest was association be-tween response and spe-cialty. Training level/expertise, practice setting, percentage of consultation caseload consisting of high-risk prostate cancer, and nationality were set as effect modifiers for multivariate logistic regression.

In total, 846 ROs and 407 urologists responded. ROs were more likely to prefer adjuvant RT (ART), ART or early salvage RT (SRT), de-

PAGE 2

Comparison of Biochemical Recurrence-Free Survival After Radical

Prostatectomy Triggered by Grade Reclassification on Active Surveillance,

and Men Newly Diagnosed with Similar Grade Disease

Diniz CP, Landis P, Carter HB,Epstein JI, Mamawala M

J Urol 24 March 2017; Article in Press

Discord Among Radiation Oncologists and

Urologists in the Postoperative Management of

High-Risk Prostate Cancer

Kishan AU, Duchesne G, Wang P-C, et al.

Am J Clin Oncol 15 March 2017; Epub

89.6% vs. 91.2%, 74.0%, 63.9%, respectively for biopsy grade group 2 (p=0.071). For biopsy grade groups ≥2, there was no significant difference in risk of BCR between groups after adjustment for age, bi-opsy extent of cancer, and PSA density.

Conclusion: AS patients re-classified to grade groups ≥2 have no greater risk of treat-ment failure as compared to men newly diagnosed with similar grades.

men in immediate RP group with diagnosis of grade groups ≥2 and grade group 2, respectively. BCR was as-sessed using Kaplan Meir analysis and a multivariate Cox model.

Results: Men on AS had lower incidence of BCR compared to men in the immediate RP groups for both biopsy grade groups ≥2 and biopsy grade group 2 (both p<0.05). One-, five-, and 10-year BCR-free survival for men in the AS vs. immediate RP was 97.9%, 76.6%, 69.0% vs. 85.5%, 65.1%, 54.2%, respectively for biopsy grade groups ≥2 (p=0.009), and 96.4%, 89.6%,

Purpose: Comparison of bio-chemical recurrence (BCR) between men in active sur-veillance (AS) undergoing radical prostatectomy (RP) triggered by grade reclassifi-cation, and men diagnosed with similar grade disease undergoing immediate RP.

Methods: We conducted a retrospective analysis of men undergoing RP from 1995-2015 at Johns Hopkins and identified four groups; 94 and 56 men in AS that under-went RP following reclassifica-tion to Gleason ≥ 7 (3+4) [grade groups ≥2] and Gleason 7 (3+4) [grade group 2], re-spectively; 3,504 and 1,979

Men Uncertain About

Risks and Benefits of

PSA Screening

USPSTF Statement May be Partly to Blame

About one-third of U.S. men surveyed said their doctor never talked with them about the pros and cons of prostate-specific antigen (PSA) screening before they were tested, researchers reported.

Among more than 200,000 men in the analytic sample, 37% were told about only advantages of PSA screening compared to 30% of men who were advised about both advantages and disad-vantages, according to George Turini III, MD, of Brown University in Provi-dence, RI, and colleagues.

Also, the proportion of unin-formed men increased slightly, but significantly, from 30% in 2012 to nearly 34% in 2014 (P<0.01), they wrote in an article in press published online ahead of print in Urology on 18 March 2017.

The study “demonstrates a potentially concerning trend



Vitamin D supplements cure everything right? Wrong! Vi-tamin D is overrated, but that does not mean that it still cannot help some folks. Re-gardless, in women, the sup-plements just failed to pre-vent cancer and just also failed a major study to pre-vent cardiovascular disease,1,2 but all is not lost! The results of one of the best clinical tri-als is expected in 2017.3 So stay tuned you vitamin D lov-ers and read this column for the true untold story of all of these clinical trials (cue the dramatic music)!

Why does Moyad write about vitamin D so much!? Why do people back their cars into a parking spot while others are waiting to park? Why do peo-ple talk on their cell phone while in an elevator? I have no idea, but the reason we need to keep up with the vita-min D research is due to the fact that it gets so much bi-ased positive attention and, when big studies show no benefit, it gets minimal atten-tion, so let’s change that now. A total of over 2,300 post-menopausal women taking 2000 IU of vitamin D3 and 1,500 mg of calcium per day vs. placebo for four years had no reduction in cancer com-pared to a placebo. Still, the average person in this study already had a normal level of vitamin D in their blood be-fore the study started, so per-haps this does not answer the ultimate question of whether supplements reduce cancer risk or slow cancer progres-sion in people that have low levels of vitamin D in their blood. However, then along came a major clinical trial of participants from Auckland, New Zealand receiving an oral

Doc Moyad’s What Works & What is Worthless Column, Also Known As “No Bogus Science” Column

“Vitamin D = Bad Start to 2017, but VITAL Results will be Available Soon?!” Mark A. Moyad, MD, MPH, University of Michigan Medical Center, Department of Urology

Editor’s Note: Us TOO invites certain physicians and others to provide information and commentary for the Hot SHEET to enrich its content to empower the reader. This column contains the opinions and thoughts of its author and are not necessarily those of Us TOO International.

vitamin D3 in an initial dose of 200,000 IU, followed a month later by once a month doses of 100,000 IU (average of over 3,300 IU/day) or placebo for a median of 3.3 years in over 5,000 individuals. The average age was approximately 66 years old and 58% were men. And, regardless of vitamin D deficiency or not, there was no difference in the rate of cardiovascular disease events between vitamin D and pla-cebo. Still, the criticism will be that daily doses are more effective than monthly doses. Yet, all is not lost because vitamin D has another major clinical trial coming out, po-tentially in 2017. It will look at daily vitamin D and cancer risk (called “VITAL” or VITa-min D and OmegA-3 Trial) with over 25,000 participants (mean age 67 years and 50% women). It could be the make it or break it study for vitamin D and/or even fish oil and

overall health. If it is negative, or no benefit is found, then vitamin D may have a history similar to selenium. If posi-tive, then it will be one of the most profound findings for a supplement in my lifetime!

Place your bets! Regardless, “first do no harm” and “less is more” is the Moyad Mantra until the results of VITAL be-come available. Now, let’s talk about what gets missed in all these vitamin D studies! The average person in these stud-ies is obese or almost obese and over half have been diag-nosed with hypertension and are taking medication for it in the U.S. VITAL study! These studies are just reflections of the current state of health in the U.S. and around the world of so-called “healthy people.” I just wish someone would design a study whereby re-ducing weight or blood pres-sure for example through diet/lifestyle would go against

PAGE 3

vitamin D or other highly- touted pills. Dreamers have to dream!

References:

1. Lappe J, Watson P, Travers-Gustafson D, et al. Effect of vitamin D and calcium supplementation on cancer incidence in older women: A random-ized clinical trial. JAMA 2017; 317:1234-1243.

2. Scragg R, Stewart AW, Waayer D, et al. Effect of monthly high-dose Vita-min D supplementation on cardiovascular disease in the Vitamin D assessment study: A randomized clini-cal trial. JAMA Cardiol 5 April 2017; Epub.

3. Bassuk S, Manson J, Lee I, et al. Baseline characteris-tics of participants in the VITamin D and OmegA-3 Trial (VITAL). Contemp Clin Trials 2016; 47:235-243.

Intermediate-Term Outcomes of Men with Very Low/Low- and

Intermediate/High-Risk Prostate Cancer Managed by Active Surveillance

Nyame YA, Almassi N, Haywood SC, et al.

J Urol 24 March 2017; Article in Press

Purpose: To compare intermediate-term clinical outcomes among men with favorable-risk and intermediate/high-risk prostate cancer (PCa) managed with active surveillance (AS).

Materials and Methods: Since 2002, 635 men with localized PCa have been managed with AS at a high-volume U.S. academic hospital with a median follow-up of 50.5 months (interquartile range [IQR] 31.1-80.3). Time to event analysis was performed for our clinical endpoints.

Results: 117 men (18.4% of the cohort) had intermediate/high-risk disease. The overall five- and 10-year all-cause survival was 98% and 94%, respectively. The cumulative metastasis-free survival at five- and 10-years was 99% and 98%. To date, no cancer-specific deaths have been observed. The overall freedom from intervention was 61% and 49%, at five- and 10-years respectively. Overall, the cumulative freedom from failure of AS – defined as the development of metastasis or biochemical failure after local therapy with curative intent – was 97% and 91% at five- and 10-years, respectively. Twenty-one (9.9%) men experienced biochemical failure after deferred treat-ment and the five-year progression-free probability was 92%. Compared to men with favorable-risk disease, men with intermediate/high-risk cancer experienced no difference in metastases, surveillance failure, or curative intervention. However, higher-risk patients experienced signifi-cantly higher risk of all-cause mortality, likely reflecting patient selection factors. These conclu-sions may be limited by the small number of events and duration of our study period.



PAGE 4

USPSTF 2017 Update (Continued from page 1)

“The other thing we have now is evidence that three men who would have devel-oped metastatic PCa won’t have metastatic disease with screening,” he added. Spe-cifically, the new evidence showed that PSA screening would prevent three cases of metastatic PCa, and one or two deaths due to PCa.

ACS and AUA both welcomed the USPSTF support for indi-vidualized decision making about PSA-based PCa screen-ing.

“The draft recommendations are thoughtful and reason-able and are in direct align-ment with the AUA’s clinical practice guidelines and guidelines from most other major physician groups,” AUA president Richard K. Babayan, MD, of Boston Uni-versity, said in a statement.

He stated, “The USPSTF clearly utilized a more inclu-sive and transparent process to develop these draft rec-ommendations.” Babayan alluded to criticisms of the lack of medical specialty rep-resentation on the task force. “This process demonstrates how the task force, special-ists, patients, and the medi-cal community as a whole can work together to de-velop recommendations that better reflect the clinical and research landscapes.”

In their latest review, the USPSTF compared potential harms and benefits of PSA-based screening for men, ages 55 to 69, followed for 10 to 15 years. The panel found that for every 1,000 men screened (or offered screen-ing), 240 would have a posi-tive result. Positive results would lead to positive biop-sies in 100, and 80 of the 100 men would opt for surgery or radiotherapy (RT) – 65 imme-diately and 15 after a period of active surveillance (AS).

They observed that “Many men will learn they have a false-positive [test] result after getting a biopsy. The potential side effects of bi-opsy include pain, bleeding, and infection.”

“We have data now showing that AS can save the same number of men from dying of PCa; that there isn’t an in-creased number of deaths due to PCa with AS com-pared with radiation (RT) or surgery,” said Krist. “AS can reduce the potential harms in this whole screening-and-treatment pathway.”

ACS Chief Medical Officer Otis Brawley, MD, said he’s “thrilled” that the USPSTF, AUA, ACS, and other organi-zations are becoming more like-minded about PCa screening. The only real dif-ference is that the task force and AUA suggest that the discussions begin at age 45, whereas the ACS recom-mends starting the discus-sion at age 50.

However, Brawley empha-sized an issue often lost in the controversy about when and how to begin PSA-based screening for PCa. “I hope the lay public and the medical community understand that the harms of PCa screening are better proven than the benefits,” Brawley said. “It’s never been that there’s no benefit to PCa screening. The problem has always been these harms.”

The USPSTF recommenda-tion reflected a response to the “sea change” in American medicine; the “knee jerk” reaction of the need for im-mediate treatment; and the adoption of the option of AS for many men with early-stage PCa. Krist agreed that emerging data on AS played a role in the updated recom-mendation. (Continued on page 6)

Updated Guideline on Brachytherapy

(Continued from page 1)

The new recommendations update the systematic review and clinical practice guideline on low-dose rate (LDR) BT for men with low- or intermedi-ate-risk prostate cancer that Cancer Care Ontario pub-lished in 2013. It incorpo-rates evidence from five ran-domized clinical trials re-ported since 2013.

The guidelines sought to an-swer the following clinical questions:

In men with newly diag-nosed prostate cancer, what is the efficacy of BT alone for clinical outcomes compared with EBRT alone or radical prostatectomy (RP) alone?

In men with newly diag-nosed prostate cancer, what is the efficacy of BT combined with EBRT for clinical outcomes com-pared with BT alone, EBRT alone, or RP alone?

Among the isotopes used for LDR BT (e.g., iodine-125 [125I], palladium-103 [103Pd], and cesium-131 [131Cs]), which isotope maximizes clinical out-comes when used in men with newly-diagnosed prostate cancer?

Key Recommendations

Among all eligible patients with low-risk disease who require or who select to un-dergo active treatment, low-dose BT alone, EBRT alone, or RP should be offered. All pa-tients should be counseled about all their treatment op-tions in a balanced, objective manner, preferably from a multidisciplinary team. This recommendation is un-changed from the previous guidelines, because no new data had a bearing on this clinical question.

In the population with inter-mediate-risk prostate cancer,

men who select EBRT, with or without androgen-deprivation therapy (ADT), BT boost (either low- or high- dose) should be offered to all eligible patients. In the low-intermediate risk group (Gleason 7, PSA <10 ng/mL or Gleason 6, PSA 10 to 20 ng/mL), low-dose BT can be of-fered as monotherapy. For eligible patients with high-risk disease who are being treated with EBRT and ADT, BT boost (LDR or high-dose rate) should be offered.

Some patients in the inter-mediate- or high-risk groups may be ineligible for BT, and ADT may be given in neoad-juvant, concurrent, and/or adjuvant settings at physician discretion. Of note, the addi-tion of neoadjuvant ADT could induce cytoreduction of prostate volume sufficient to allow BT.

For men receiving low-dose BT, 125I and 103Pd are each reasonable isotope options, but no recommendation could be made for or against using 131Cs or high-dose BT.

Patients who opt for BT should only be treated at centers that follow strict quality-assurance standards, the document emphasizes.

It also notes that there may be increased genitourinary toxicity after BT vs. EBRT alone. Also, the authors note that it “cannot be deter-mined whether there is an overall or cause-specific sur-vival advantage for BT vs. EBRT alone, because none of the trials were designed or powered to detect a mean-ingful difference in survival outcomes.”

Men should be encouraged to participate in clinical trials evaluating novel or targeted therapies, the authors add.

Medscape Oncology 30 March 2017


PAGE 5

Purpose: To our knowledge the optimal treatment of patients following a negative prostate biopsy is unknown. Consequently, resources are increasingly being directed toward risk stratification in this cohort. However, the risk of prostate cancer mortality in this group before the in-troduction of supplemental biomarkers and imaging techniques is unclear.

Materials and Methods: The PLCO (Prostate, Lung, Colo-rectal and Ovarian Cancer) Screening Trial provides sur-vival data prior to the imple-mentation of new diagnostic interventions. We divided men with an initial positive screen and a subsequent prostate biopsy into cohorts based on positive or negative results. Prostate cancer-specific mortality was then compared to that in the trial control arm to estimate the prognostic significance of biopsy results relative to the general population.

Results: A total of 36,525 and 36,560 patients com-

prised the screening and con-trol arms, respectively. Of 4,064 subjects with a positive first screen, 1,233 underwent a linked biopsy, of which 473 were positive and 760 were negative. At a median fol-lowup of 12.9 years, 1.1% of men in the negative biopsy cohort had died of prostate cancer. The difference in mortality rates between the negative biopsy and control arms was 0.734 deaths per 1,000 person. The propor-tional subhazard ratios of prostate cancer-specific mor-tality for negative biopsy and positive biopsy relative to the control arm were 2.93 (95% CI 1.44–5.99) and 18.77 (95% CI 12.62–27.93), re-spectively.

Conclusions: After a negative prostate biopsy, men face a relatively low risk of death from prostate cancer when followed with traditional markers and biopsy tech-niques. This suggests limited potential for new diagnostic interventions to improve survival in this group.

Prognostic Significance of a Negative Prostate

Biopsy: An Analysis of Subjects Enrolled in a

Prostate Cancer Screening Trial

Lewicki PL, Shoag J, Golombos DM, et al.

J Urol 2017; 197: 1014-1019

Vessel-Sparing Radiotherapy


aids. Most of the sexual aids used were phosphodi-esterase-type 5 inhibitors (e.g., Viagra, Cialis, and oth-ers).

Two-thirds of men at five years reported moderate to very high confidence in the ability to achieve and keep an erection. Overall, 13 of 135 men developed bio-chemical failure (BCF), which translated into biochemical relapse-free survival rates of 99.3% at five years and 89.9% at 10 years.

Based on previously vali-dated models, this cohort would have an expected po-tency rate (able to achieve an erection firm enough for intercourse) of 42% at two years after standard external beam RT (EBRT) and 24% at two years after nerve-sparing radical prostatectomy (RP), in contrast to the actual ob-served rate of 78% here.

Among men with erections firm enough for intercourse at baseline, two-year preser-vation of EF was 87% for ves-sel-sparing RT, 69% for con-ventional EBRT, and 42% for nerve-sparing RP.

Results were similar in men receiving EBRT vs. EBRT plus

BT, but men receiving ADT generally had worse EF out-comes at two years and mod-estly recovered by five years.

“This proves that dose can be intensified to the prostate without affecting sexual out-comes,” Dr. McLaughlin said. “It validates what we term the functional anatomy approach– by defining critical adjacent functioning tissues visible on MRI and poorly visualized on CT we can in-clude these structures in the treatment plan and drastically limit dose compared to CT based plans.”

“In any man diagnosed with prostate cancer with good baseline sexual function, ves-sel-sparing RT will have a role,” he said.

“Although this study empha-sized defining and sparing criti-cal adjacent structures related to sexual function, other criti-cal functional domains, such as bladder and sphincter function and rectal and anal function, can all be mapped and spared through MRI-based planning,” Dr. McLaughlin said. “We will be reporting improved out-comes in these critical domains similar to improvements in sexual function outcomes.”

Reuters Health 9 March 2017

Magnetic Resonance Imaging in the Diagnosis of Prostate Cancer in Patients with a Total

Prostate-Specific Antigen Level of 2-10 ng/mL

Furuya K, Kawahara T, Narahara M, et al. Scand J Urol 29 March 2017; Epub ahead of print

More accurate diagnostic procedures for prostate cancer are needed to avoid unnecessary biopsy due to the low specificity of prostate-specific antigen (PSA). Recent studies showed that the percentage of serum isoform [-2]proPSA (p2PSA) to free PSA (%p2PSA), the Pros-tate Health Index (PHI) and magnetic resonance imaging (MRI) were more accurate than PSA. The aim of this study was to test the accu-racy of %p2PSA, PHI and MRI in discriminating patients with and without prostate cancer.

The subjects were 50 consecutive men with a PSA level of 2.0-10.0 ng/mL, who underwent prostate biopsy from October 2012 to July 2014. These patients underwent multiparametric MRI before biopsy, and their serum samples were measured for PSA, free PSA and %p2PSA. The sensitivity, specificity and accuracy of PHI, %p2PSA and MRI were compared with PSA in the diagnosis of biopsy-confirmed prostate cancer.

In a univariate analysis, %p2PSA [area under the curve (AUC): 0.811] and PHI (AUC 0.795) were more accurate than MRI (AUC: 0.583) and PSA (AUC: 0.554) for prostate cancer detection. At 60% sensitivity, the specificity of PHI (76.5%) was higher than that of MRI (52.9%). For significant cancer detection, %p2PSA (AUC: 0.745), PHI (AUC: 0.791) and MRI (AUC: 0.739) were marginally more accurate than PSA (AUC: 0.696). At 85% sensitivity, the specificity of MRI (62.1%) was higher than that of PHI (34.5%).

PHI and %p2PSA can be used for screening the general population and MRI can be used for detection of significant cancer in patients sus-pected, from screening tests, of having prostate cancer.


PAGE 6

in the quality of pre-PSA screening discussions that men are having with health-care practitioners before blood work is drawn,” they stated. “While some litera-ture has proposed that shorter office visit times re-lated to high patient volumes and increased practice de-mands may provide sufficient explanation as to why clini-cians are not routinely talking to all men about both the advantages and disadvan-tages of PSA testing, we be-lieve the true explanation is likely much more complex.”

The authors said a 2012 statement from the United States Preventive Services Task Force (USPSTF) may be part of the explanation. The statement recommends against PSA screening for the general population, citing the potential harms associated with complications of screen-ing and overdiagnosis.

“The USPSTF report very clearly dissuades clinicians from recommending routine PSA screening in healthy males, and we believe our findings may be indicative of a shift in practice patterns away from detailed pre-screening discussions among healthcare practitioners who have implemented the USPSTF recommendation into their caregiving,” they wrote.

In an editorial comment, Simon Kim, MD, MPH, of Case Western Reserve Uni-versity School of Medicine in Cleveland, and colleagues agreed with that assessment.

“To a large degree, this clini-cal debate is attributable to the marked disagreement ranging from the USPSTF issuing a Grade D recommen-dation against prostate can-cer screening for all men at average risk for prostate can-cer contrasted to the Ameri-can Urological Association,

American Cancer Society, and the National Compre-hensive Cancer Network en-dorsing shared decision mak-ing about reviewing the mer-its of screening and eliciting patient preferences into the decision for early detection of prostate cancer,” Kim’s group wrote.

“At this time of uncertainty regarding prostate cancer screening, it is now more important for patients and providers to engage in thoughtful discussions about the risks and benefits of a PSA test and incorporate shared decision making into the clinical encounter,” they advised.

Turini’s group analyzed data from 217,053 men who par-ticipated in the 2012 and 2014 Behavioral Risk Factor Surveillance System (BRFSS) surveys. These telephone surveys were administered by state health departments using a standardized ques-tionnaire. Approximately 80% of the men surveyed were white, 9% were black, and 8% Hispanic.

In 2012, before the task force made its recommendation, 30.5% of the men surveyed reported discussing neither the advantages nor disadvan-tages of screening with their healthcare provider; 30.1% said they discussed both, 38.5% discussed only advan-tages, and 0.8% discussed only disadvantages. In 2014, after the recommendation, 33.9% reported discussing neither pros nor cons while 29.5% discussed both, 35.7% only talked about advan-tages, and 0.8% only talked about disadvantages.

In 2012, black men were twice as likely to have dis-cussed both advantages and disadvantages with their healthcare provider com-pared with white men

Of the 100 men with a posi-tive biopsy, “20-50% will have cancer that never grows, spreads, or harms them.” Of the 80 men who opt for definitive treatment, “60 or more will experience serious complications [including] urinary inconti-nence and/or impotence.”

Despite support for discus-sion-driven decision making, a recent study showed that a third of men did not discuss the pros and cons of PSA tests with clinicians prior to testing. Krist said the findings disappointed but did not surprise him.

“Only by incorporating men’s values and preferences into the decision-making process can we make the right deci-sion,” he said. “It’s extremely important for physicians to discuss this with patients, and patients really shouldn’t be getting a PSA test without understanding the benefits and the harms.”

USPSTF did not change its recommendation against PSA-based screening for PCa in men ages ≥70.

MedPage Today 11 April 2017

USPSTF 2017 Update


Men Uncertain About Risks and Benefits of PSA Screening (Continued from page 2)

(relative risk ratio 2.07, 95% CI 1.84-2.34, P<0.01). That figure didn’t change much in 2014 (relative RR 1.95, 95% CI 1.76-2.18, P<0.01), the study found.

“We feel this finding is en-couraging on multiple levels,” the investigators said. “First, it suggests that general health-care providers, represented in the BRFSS, appreciate pub-lished literature identifying not only a higher prevalence of prostate cancer among certain populations (in this case, African American men) but also a higher risk of mor-tality, and consequently a need to provide more educa-tional information about ad-vantages and disadvantages of PSA testing to those men.”

A study limitation was that it didn’t distinguish between first time PSA checks and annual screening tests. “If healthcare practitioners more frequently discuss ad-vantages and disadvantages with a patient prior to his first PSA test than before subsequent routine screen-ing, our finding that men were less likely to receive comprehensive counseling in 2014 relative to 2012 may be more accurately explained by a higher percentage of re-peat screening tests than a true shift away from appro-priate pre-screening advice,” the authors acknowledged.

Nevertheless, “the trend we’ve identified towards a large number of patients undergoing PSA testing with-out any counseling about either [sic] advantages or disadvantages should not only be viewed as a serious problem but acted upon swiftly so as to minimize the chances of cultivating a growing cohort of patients ill-prepared to handle the re-percussions of prostate can-cer screening,” they stated.

nodal RT. These differences are likely to create a sense of dissonance for patients, which may, in turn, explain the underutilization of post-operative RT in general urological practice.

Post-RP Management


Conclusions: Patients with localized prostate cancer on AS demonstrated a low rate of AS failure, PCa-specific mortality, metastases, re-gardless of baseline risk.

Intermediate-Term



PAGE 7

Doctor Chodak’s Bottom Line

Gerald Chodak, MD, Author, Winning the Battle Against Prostate Cancer, Second Edition http://www.prostatevideos.com/

Editor’s Note: Us TOO has invited certain physicians and others to provide information and commentary for the Hot SHEET to enrich its content to empower the reader. This column contains the opinions and thoughts of its author and are not necessarily those of Us TOO International.

P1, “USPSTF Backs…” Since development of PSA, screen-ing for prostate cancer has been a major controversy. For many years the message was strongly in favor of doing the test with little discussion of its shortcomings. Based on randomized studies, the USPSTF has issued changes in its guidelines. Prior to 2012 and even afterward, Turini et al. has found that less than one-third of men were being given proper counseling. Ei-ther only the benefits were discussed or nothing was pre-sented. So, at present, about 70% of men are not being given proper counseling. Sur-prisingly, African American men were twice as likely to receive proper counseling. Regardless of the reason, clearly the problem is that men are not being informed to make an educated decision about what to do. This issue is likely to be re-addressed be-cause of the new guideline about to be released. They have changed their recom-mendation from level D (against screening) to Level C (the harms and benefits are about equal). They now ad-vise counseling for all men between 55-69 about the risks and benefits so they can make an informed decision. This change is likely to pre-sent doctors with a greater challenge and efforts are needed to make this an easy transition. One option would be to develop a standardized informed consent form for screening that EVERY man reviews and signs before de-ciding what to do. It would make the doctor’s job easier while insuring that all men get the same basic information throughout the U.S.

The Bottom Line: Men have not been given proper coun-

seling about the pros and cons of screening for pros-tate cancer and, with the new recommendation about to be published, something is needed to help this process.

P1, “Update Guideline on…” The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario have issued a joint clinical practice guideline update on the use of brachytherapy (BT) for prostate cancer patients. The new guideline was published online in the Journal of Clini-cal Oncology on March 27th. The major change is for men with intermediate-risk dis-ease. Unfortunately, they have made a recommenda-tion that says all men who receive external beam radio-therapy (EBRT) should also be offered a boost with high dose RT or BT. This is based on results from several ran-domized trials, however, none of them used survival as an end point; they only used biochemical or clinical recurrence. Side effects with combined therapy are higher compared to EBRT alone. One should strongly question whether the absence of sur-vival data justifies this new recommendation. Certainly, men being offered the ther-apy should be made aware of this limitation. For studies on surgery and even monother-apy studies of EBRT, survival has been the outcome needed to make a strong recommendation, so this is a weakness of the new guide-line.

The Bottom Line: New rec-ommendations for combin-ing BT with EBRT for interme-diate- and high-risk disease are not based on survival as an outcome and would ap-pear to be premature.

P1, “Vessel-Sparing RT…” Can RT be modified to spare the vessels responsible for EF? McLaughlin and co-workers addressed this ques-tion in a non-randomized study. They spared the cor-pus cavernosum and internal pudendal artery in 144 men given external beam RT alone, or in combination with brachytherapy (BT). Com-pared to historical results, they observed a higher rate of sexual function at two years and five years using this approach. Importantly, the PSA failure rate was very low. This is potentially impor-tant information but it needs additional validation in a randomized study.

The Bottom Line: Vessel sparing RT has the potential to reduce erectile dysfunc-tion, but before widespread adoption the findings need to be validated in a prospec-tive randomized study.

P2, “Comparison of…” As active surveillance (AS) be-comes increasingly accept-able to patients and doctors, an unanswered question is whether there is a long-term risk to delaying therapy. As yet, no randomized data are available. The new report by Diniz et al. attempts to add new information. They com-pared men who received immediate radical prostatec-tomy (RP) to those who had an upgrading after some time on AS. They found no significant difference in bio-chemical failure for the men given immediate RP for Glea-son 3+4 or higher disease compared to those getting delayed treatment. Does this prove the safety of AS? Not really, because the study was not randomized and PSA recurrence is not a good out-come measure. Unfortu-

nately, a proper study will be difficult to design. The means would be to prospectively collect data on those getting immediate vs. delayed RP and then follow those men long enough to measure sur-vival. Until then, it will re-main an open question whether AS with delayed therapy poses any added risk to men compared to immedi-ate treatment.

The Bottom Line: The long-term safety of AS, followed by RP, compared to immedi-ate therapy remains un-known.

P2, “Discord Among…” Past studies have demonstrated a specialty-related bias regard-ing treatment recommenda-tions for prostate cancer; surgeons have in general preferred radical prostatec-tomy (RP) and radiation on-cologists have preferred RT. Additional bias is demon-strated in the report by Kishan and co-workers who obtained written surveys regarding the use of adjuvant and salvage RT after RP. They found radiation oncologists were more likely to recom-mend adjuvant RT and earlier salvage RT. Randomized studies do support adjuvant RT in high-risk patients, since the odds of benefitting are around 1 in 10. Similarly, the odds of benefitting from sal-vage RT are very low. Given the difference in approaches by the different specialists, it is critical that both groups provide a balanced presenta-tion between risks and bene-fits so that men can share in the decision rather than rely on the individual biases of the treating physician.

The Bottom Line: Urologists and radiation oncologists


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men who are being screened. Other reports found that men often undergo multiple biop-sies during follow-up. This study suggests that little follow-up may be needed if the first prostate biopsy is nega-tive.

The Bottom Line: Screened men with one negative pros-tate biopsy may need little follow-up because the even-tual risk of dying from pros-tate cancer is very low, but more data are needed to con-firm this finding.

P5, “Magnetic…” Many arti-cles have been written about the shortcomings of the PSA test for prostate cancer screening. Other methods are being evaluated including se-rum isoform [-2]proPSA (p2PSA) to free PSA (%p2PSA), the Prostate Health Index (PHI) and magnetic resonance imag-ing (MRI) with some studies suggesting better accuracy than PSA. In a small study by Furuya of only 50 men under-going biopsy, each of these parameters was used. They found that %p2PSA and PHI were more accurate than MRI

Doctor Chodak’s Bottom Line (Continued from page 7)

have different attitudes about recommending adju-vant and salvage RT after RP, which means both groups need to give patients ade-quate information so they can make a shared decision.

P3, “Intermediate-Term…” Another study on AS is being reported by Nyame et al. who followed 635 men over a me-dian follow-up of five years. About 20% had intermediate/high-risk disease. At five and 10 years, 61% and 49% did not have treatment interven-tion. Freedom from metasta-ses or biochemical failure was very high at five and 10 years. These results add to the body of data confirming that men on AS have a low risk of pro-gression with about half able to avoid local therapy. This cohort needs longer follow-up to know what fraction of the high-risk men will need intervention or suffer disease progression. If most ulti-mately need treatment or a significant fraction develop metastatic disease, a ques-tion can be raised about how

much benefit occurred to those men by waiting for therapy.

The Bottom Line: Longer follow-ups are needed in the cohort of intermediate/high- risk disease to know whether AS truly enables a proportion of them to avoid local ther-apy while preserving long-term outcomes.

P5, “Prognostic…” One of the problems with screening for prostate cancer is the need for repeat testing, including repeat biopsies over time. Lewicky and co-workers asked an important question; what is the risk of eventually dying from prostate cancer after having one negative biopsy? They looked at men who had a negative biopsy in the PLCO trial and found that at nearly 13 years, only 1.1% died of prostate cancer if their initial biopsy was negative. What is unclear from the abstract is what fraction of men had mul-tiple biopsies and what fraction ended up with a diagnosis of prostate cancer. This finding has important implications for

for detecting prostate cancer while PSA had the lowest accu-racy. Their conclusion is that PHI and %p2PSA can be used for screening the general population. Unfortunately, their findings are far too pre-mature to make such a conclu-sion. They need to provide information about the positive and negative predictive values for the tests so estimates of detection in a broad popula-tion can be determined. Ulti-mately, if those look favorable, a recommendation to use any of them for screening would need the same kind of pro-spective randomized study as was done for PLCO.

The Bottom Line: Very pre-liminary data suggest that PHI and %p2PSA may be better than PSA for detecting pros-tate cancer, but more investi-gation is needed before either can be considered as a re-placement screening test for PSA.

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